Many types of ligand-receptor assays have been used to detect the presence of various substances in body fluids, such as urine, saliva, or blood. Many of these assays are designed to make a quantitative determination, but in many circumstances all that is required is a qualitative positive/negative indication. Examples of such qualitative assays include blood typing, pregnancy testing, and many types of urinalysis. For these tests, visually observable indicia, such as the presence of agglutination or a color change, are preferred.
Qualitative ‘positive/negative’ assays require a high degree of sensitivity due to the often low concentration of the ligand of interest present in the test fluid. False positives can be troublesome, particularly with agglutination and other rapid detection methods such as dipstick and color change tests. Because of these problems, sandwich assays and other sensitive detection methods which use metal sols or other types of colored particles have been developed.
A common type of device that incorporates the use of such biological interactions is a test strip assay device. U.S. Pat. No. 6,485,982, which is incorporated herein by reference in its entirety, describes a diagnostic device formed of an elongate outer casing which houses an interior permeable material (such as fiber glass) capable of transporting an aqueous solution by capillary action, wicking, or simple wetting. The casing defines a sample inlet, and interior regions, which are designated as a test volume and a reservoir volume. The reservoir volume is disposed in a section of the test cell spaced apart from the inlet and is filled with sorbent material. The reservoir acts to receive liquid transported along a flow path defined by the permeable material and extending from the inlet and through the test volume. In the test volume is a test site comprising a first protein having a binding site specific to a first epitope of the ligand immobilized in fluid communication with the flow path (e.g., bound to the permeable material or to latex particles entrapped in or bonded to the permeable material). A window, such as a hole or transparent section of the casing, permits observations of the test site through the casing wall. The method of use of the test cell requires the use of a conjugate comprising a second protein bound to colored particles, such as a metal sol or colloid, preferably gold. U.S. Pat. No. 7,045,342, which is incorporated herein by reference in its entirety, describes an improved diagnostic device including a test strip comprising of a biphasic chromatographic medium. The biphasic chromatographic medium is formed of a release medium joined to a capture medium located downstream of the release medium. The release and capture media preferably comprise two different materials, or phases, having different specific characteristics. The two phases are joined together to form a single liquid path such that a solvent front can travel unimpeded from the proximal (upstream) end of the release medium to the distal (downstream) end of the capture medium.
A purely visual (i.e., human eye dependent) diagnostic test as exemplified above requires proper interpretation of the results. However, devices have been developed to provide an automated detector system for determining sufficient color development at a test site and for also ensuring that the color intensity is read/interpreted at the appropriate time after sample application. For example, U.S. Pat. No. 5,837,546 discloses an integrated reader and a test-strip wherein the test strip is provided with additional electrodes which sense the presence of fluid on the test strip which generates a signal to switch on the sensing electronics. The device includes a housing having an exterior surface and defining an interior area. A sample receptor receives the sample. Reagents on a test strip react with the sample to yield a physically detectable change which correlates with the amount of selected analyte in the sample. A detector responds to the physically detectable change and produces an electrical signal which correlates to the amount of the selected analyte in the sample. A processor converts the electrical signal to a digital output. In another example, U.S. Pat. No. 7,220,597 discloses an integrated reader with a test-strip activated by a mechanical switch means, wherein the switch means is responsive to the removal of a lid from the device housing. The device also requires a sample sensor for detecting the presence of the sample, wherein sample presence signal generates a time delay, and a reaction sensor responsive to the time delay for detecting an analyte in the fluid sample.
Although diagnostic devices, such as those described above, show improvements over the art, there still remains a need for test devices providing greater accuracy and sensitivity. For example, in the field of pregnancy testing, accurate and rapid detection of low levels of hCG is desired to allow consumers to confirm pregnancy soon after conception has occurred.